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Ginsenoside Rk1 inhibits HeLa cell proliferation through an endoplasmic reticulum signaling pathway

  • Qiuyang Li;Hang Sun;Shiwei Liu;Jinxin Tang;Shengnan Liu;Pei Yin;Qianwen Mi;Jingsheng Liu;Lei yu;Yunfeng Bi
    • Journal of Ginseng Research
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    • v.47 no.5
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    • pp.645-653
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    • 2023
  • Background: Changes to work-life balance has increased the incidence of cervical cancer among younger people. A minor ginseng saponin known as ginsenoside Rk1 can inhibit the growth and survival of human cancer cells; however, whether ginsenoside Rk1 inhibits HeLa cell proliferation is unknown. Methods and results: Ginsenoside Rk1 blocked HeLa cells in the G0/G1 phase in a dose-dependent manner and inhibited cell division and proliferation. Ginsenoside Rk1 markedly also activated the apoptotic signaling pathway via caspase 3, PARP, and caspase 6. In addition, ginsenoside Rk1 increased LC3B protein expression, indicating the promotion of the autophagy signaling pathway. Protein processing in the endoplasmic reticulum signaling pathway was downregulated in Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, consistent with teal-time quantitative PCR and western blotting that showed YOD1, HSPA4L, DNAJC3, and HSP90AA1 expression levels were dramatically decreased in HeLa cells treated with ginsenoside Rk1, with YOD1 was the most significantly inhibited by ginsenoside Rk1 treatment. Conclusion: These findings indicate that the toxicity of ginsenoside Rk1 in HeLa cells can be explained by the inhibition of protein synthesis in the endoplasmic reticulum and enhanced apoptosis, with YOD1 acting as a potential target for cervical cancer treatment.

An EST survey of genes expressed in liver of rock bream(Oplegnathus fasciatus) with particular interests on the stress-responsive and immune-related genes

  • Park, Byul-Nim;Park, Ji-Eun;Kim, Ki-Hong;Kim, Dong-Soo;Nam, Yoon-Kwon
    • Proceedings of the Korean Aquaculture Society Conference
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    • 2003.10a
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    • pp.43-43
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    • 2003
  • EST analysis was performed to identify stress-responsive and immune-related genes from rock bream (Oplegnathus fasciatus). cDNA libraries were constructed with liver and randomly chosen 624 clones were subjected to automated sequence analysis. Of 624 clones sequenced in total, approximately 15% of ESTs was novel sequences (no match to GenBank) or sequences with high homology to hypothetical/unknown genes. The bioinforamtic sequence analysis including functional clustering, homology grouping, contig assembly with electronic northern and organism matches were carried out. Several potential stress-responsive biomarker and/or immune-related genes were identified in all the tissues examined. It included lectins, ferritins, CP450, proteinase, proteinase inhibitors, anti-oxidant enzymes, various heat-shock proteins, warm temperature acclimation protein, complements, methyltransferase, zinc finger proteins, lysozymes, macrophage maturation associated protein, and others. This information will offer new possibilities as fundamental baseline data for understanding and addressing their molecular mechanism involved in host defense and immune systems of this species.

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Ginseng saponins and the treatment of osteoporosis: mini literature review

  • Siddiqi, Muhammad Hanif;Siddiqi, Muhammad Zubair;Ahn, Sungeun;Kang, Sera;Kim, Yeon-Ju;Sathishkumar, Natarajan;Yang, Dong-Uk;Yang, Deok-Chun
    • Journal of Ginseng Research
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    • v.37 no.3
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    • pp.261-268
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    • 2013
  • The ginseng plant (Panax ginseng Meyer) has a large number of active ingredients including steroidal saponins with a dammarane skeleton as well as protopanaxadiol and protopanaxatriol, commonly known as ginsenosides, which have antioxidant, anticancer, antidiabetic, anti-adipocyte, and sexual enhancing effects. Though several discoveries have demonstrated that ginseng saponins (ginsenosides) as the most important therapeutic agent for the treatment of osteoporosis, yet the molecular mechanism of its active metabolites is unknown. In this review, we summarize the evidence supporting the therapeutic properties of ginsenosides both in vivo and in vitro, with an emphasis on the different molecular agents comprising receptor activator of nuclear factor kappa-B ligand, receptor activator of nuclear factor kappa-B, and matrix metallopeptidase-9, as well as the bone morphogenetic protein-2 and Smad signaling pathways.

Epac2 contributes to PACAP-induced astrocytic differentiation through calcium ion influx in neural precursor cells

  • Seo, Hyunhyo;Lee, Kyungmin
    • BMB Reports
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    • v.49 no.2
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    • pp.128-133
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    • 2016
  • Astrocytes play a critical role in normal brain functions and maintaining the brain microenvironment, and defects in astrocytogenesis during neurodevelopment could give rise to severe mental illness and psychiatric disorders. During neuro-embryogenesis, astrocytogenesis involves astrocytic differentiation of neural precursor cells (NPCs) induced by signals from ciliary neurotrophic factor (CNTF) or pituitary adenylate cyclase-activating peptide (PACAP). However, in contrast to the CNTF signaling pathway, the exact mechanism underlying astrocytic differentiation induced by PACAP is unknown. In the present study, we aimed to verify a signaling pathway specific to PACAP-induced astrocytogenesis, using exchange protein directly activated by cAMP2 (Epac2)-knockout mice. We found that PACAP could trigger astrocytic differentiation of NPCs via Epac2 activation and an increase in the intracellular calcium concentration via a calcium ion influx. Taken together, we concluded that astrocytogenesis stimulated by PACAP occurs through a novel signaling pathway independent from CNTF-JAK/STAT signaling, that is the well-known pathway of astrocytogenesis.

The primary cilium as a multiple cellular signaling scaffold in development and disease

  • Ko, Hyuk-Wan
    • BMB Reports
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    • v.45 no.8
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    • pp.427-432
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    • 2012
  • Primary cilia, single hair-like appendage on the surface of the most mammalian cells, were once considered to be vestigial cellular organelles for a past century because of their tiny structure and unknown function. Although they lack ancestral motility function of cilia or flagella, they share common ground with multiciliated motile cilia and flagella on internal structure such as microtubule based nine outer doublets nucleated from the base of mother centrioles called basal body. Making cilia, ciliogenesis, in cells depends on the cell cycle stage due to reuse of centrioles for cell division forming mitotic spindle pole (M phase) and assembling cilia from basal body (starting G1 phase and maintaining most of interphase). Ciliary assembly required two conflicting processes such as assembly and disassembly and balance between these two processes determines the length of cilia. Both process required highly conserved transport system to supply needed substance to grow tip of cilia and bring ciliary turnover product back to the base of cilia using motor protein, kinesin and dynein, and transport protein complex, IFT particles. Disruption of ciliary structure or function causes multiple human disorder called ciliopathies affecting disease of diverse ciliated tissues ranging from eye, kidney, respiratory tract and brain. Recent explosion of research on the primary cilia and their involvement on animal development and disease attracts scientific interest on how extensively the function of cilia related to specific cell physiology and signaling pathway. In this review, I introduce general features of primary cilia and recent progress in understanding of the ciliary length control and signaling pathways transduced through primary cilia in vertebrates.

Inhibitory Mechanism of Curcumin in Osteoclast Differentiation (파골세포의 분화에 커규민의 억제 작용기전)

  • Kwak, Han-Bok;Choi, Min-Kyu
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.22 no.4
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    • pp.796-801
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    • 2008
  • Bone is a dynamic tissue that is regulated by the balance between bone-resorbing osteoclasts and bone-forming osteoblasts. Curcumin isolated from Kang-hwang (Turmeric) is widely used as a foodstuff, cosmetic, and medicine. However, the effect of curcumin isolated from Kang-hwang in osteoclast differentiation remains unknown. In this study, we sought to examine the role of curcumin in osteoclast differentiation. Here we show that curcumin greatly inhibited RANKL-mediated osteoclast differentiation in osteoclast precursors without cytotoxicity. RANKL induced the phosphorylation of p38 and JNK mitogen-activated protein kinase (MAPK) and mediated $I-{\kappa}B$ degradation in bone marrow macrophages (BMMs). However, RANKL-mediated p38 MAPK phosphorylation was inhibited by the addition of curcumin. Curcumin inhibited the mRNA expression of TRAP, c-Fos, and NFATc1 in BMMs treated with RANKL. Furthermore, the protein expression of c-Fos and NFATc1 induced by RANKL was suppressed by curcumin treatment. Taken together, our results suggest that curcumin may have a potential therapeutic role in bone-related diseases such as osteoporosis by inhibiting osteoclast differentiation.

Studies of Anti-inflammation of Liriopis Tuber to Autoimmunune Diabetes in NOD Mice (NOD 당뇨병 생쥐에 미치는 맥문동의 항염증 효과)

  • Roh, Seong-Soo;Choi, Hak-Joo;Kim, Dong-Hee;Seo, Young-Bae
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.22 no.4
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    • pp.766-770
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    • 2008
  • Bone is a dynamic tissue that is regulated by the balance between bone-resorbing osteoclasts and bone-forming osteoblasts. Curcumin isolated from Kang-hwang (Turmeric) is widely used as a foodstuff, cosmetic, and medicine. However, the effect of curcumin isolated from Kang-hwang in osteoclast differentiation remains unknown. In this study, we sought to examine the role of curcumin in osteoclast differentiation. Here we show that curcumin greatly inhibited RANKL-mediated osteoclast differentiation in osteoclast precursors without cytotoxicity. RANKL induced the phosphorylation of p38 and JNK mitogen-activated protein kinase (MAPK) and mediated $I-{\kappa}B$ degradation in bone marrow macrophages (BMMs). However, RANKL-mediated p38 MAPK phosphorylation was inhibited by the addition of curcumin. Curcumin inhibited the mRNA expression of TRAP, c-Fos, and NFATc1 in BMMs treated with RANKL. Furthermore, the protein expression of c-Fos and NFATc1 induced by RANKL was suppressed by curcumin treatment. Taken together, our results suggest that curcumin may have a potential therapeutic role in bone-related diseases such as osteoporosis by inhibiting osteoclast differentiation.

Studies on the Comparison of Physicochemical Properties and the Presumption of Sensory Quality of Japonica Rice Varieties Cultivated in Korea and Japan (한국과 일본의 자포니카종 쌀에 대한 이화학적 특성의 비교 및 관능품질의 추정에 관한 연구)

  • 홍원표;이성갑;박승남
    • The Korean Journal of Food And Nutrition
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    • v.14 no.6
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    • pp.596-604
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    • 2001
  • Twelve varieties of Korean rice and ten varieties of Japanese rice were selected. After being milled. they were analyzed about various physicochemical properties such as moisture, protein and amylose, a -amylase activity, gelatinization properties. And after being cooked with proper amount of water texture and other physical properties were measured by Texturometer, Tensipresser and Rheolograph-micro. Finally the sensory evaluation test was carried out. The results were as follows. 1. In case of protein contents, amylose contents and $\alpha$-amylase activity, Korean rice had a slightly higher value than Japanese As a consequence. Korean rice showed a little stronger hardness and a little weaker stickiness compared with Japanese rice. 2. Amylose contents showed very high correlation with other physicochemical properties and peak viscosity and gelatinization temperature of RVA, the ratio of stickiness to hardness( -Hl/Hl ) of Texturometer and the tan $\delta$(the ratio of dynamic loss to dynamic viscoelasticity) of Rheolograph-micro showed high correlation with other analyzed properties. 3. The ( -/+)work balance of low compression test(25% ) of Tensipresser analysis(texture analysis on the surface of cooked rice) and tan f of Rheolograph-micro showed very high correlation with sensory evaluation results. By using this parameters as major independent variables, some trials to derive high confidence multiple regression equations were accomplished. By the equations it would be possible to make an approximate pre-estimate of eating quality for unknown japonica rice.

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Identification of Differentially Expressed Proteins in Imatinib Mesylate-resistant Chronic Myelogenous Cells

  • Park, Jung-Eun;Kim, Sang-Mi;Oh, Jong-K.;Kim, Jin-Y.;Yoon, Sung-Soo;Lee, Dong-Soon;Kim, Young-Soo
    • BMB Reports
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    • v.38 no.6
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    • pp.725-738
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    • 2005
  • Resistance to imatinib mesylate (also known as Gleevec, Glivec, and STI571) often becomes a barrier to the treatment of chronic myelogenous leukemia (CML). In order to identify markers of the action of imatinib mesylate, we used a mass spectrometry approach to compare protein expression profiles in human leukemia cells (K562) and in imatinib mesylate-resistant human leukemia cells (K562-R) in the presence and absence of imatinib mesylate. We identified 118 differentially regulated proteins in these two leukemia cell-lines, with and without a $1\;{\mu}M$ imatinib mesylate challenge. Nine proteins of unknown function were discovered. This is the first comprehensive report regarding differential protein expression in imatinib mesylate-treated CML cells.

Ceramide-Mediated Cell Death Was Accompanied with Changes of c-Myc and Rb Protein

  • Moon, Soon-Ok;Lee, Jin-Woo
    • BMB Reports
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    • v.31 no.4
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    • pp.333-338
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    • 1998
  • The sphingomyelin cycle and ceramide generation have been recognized as potential growth suppression signals in mammalian cells. Ceramide has been shown to induce differentiation, cell growth arrest, senescence, and apoptosis. Although the intracelluar target for the action of ceramide remains unknown, recent studies have demonstrated the role of cytosolic ceramideactivated protein phosphatase(CAPP). In this study, the cytotoxic effect of C2-ceramide, a synthetic cellpermeable ceramide analog, on HEp-2 cells and the mechanism by which ceramide induces cell death were investigated. The addition of exogenous C2-ceramide resulted in a concentration dependent cell death. Okadaic acid, a potent inhibitor of CAPP, enhanced ceramide-mediated cell death, which suggests that CAPP is not involved in this process. To understand the mechanism of action of ceramide, we studied the relationship between ceramide and c-Myc and pRb which are defined components of cell growth regulation. Western blot analyses revealed that C2-ceramide (10${\mu}M$) induced c-Myc down-regulation, but there were no significant changes in pRb. However, treatment of okadaic acid (10 nM) enhanced c-Myc and pRb down-regulation. Reduction of the amount of c-Myc and pRb occurred during HEp-2 cell death. These results suggest that the cytotoxic effect of ceramide in HEp-2 cells may not be mediated through the action of CAPP and that the downstream target for ceramide is c-Myc and pRb.

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